Nerve capping with a nerve conduit for the treatment of painful neuroma in the rat sciatic nerve
Nerve capping with a nerve conduit for the treatment of painful neuroma in the rat sciatic nerve
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DOI：
10.3171/2018.10.jns182113
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发表时间：
2020-03-01
影响因子：
4.1
通讯作者：
Nakamura, Hiroaki
中科院分区：
文献类型：
--
作者：
Onode, Ema;Uemura, Takuya;Nakamura, Hiroaki
目的：尽管有许多外科手术方法，但治疗疼痛性神经瘤仍然很困难。近年来，人工神经导管神经盖治疗疼痛性神经瘤已被引入临床和基础研究。然而，神经导管的适当长度和疼痛缓解机制尚未确定。在这项研究中，作者旨在研究生物可吸收神经导管在大鼠坐骨神经截肢模型中的神经盖治疗。通过组织学分析，作者重点研究了神经导管长度和疼痛缓解机制。方法16只Sprague Dawley大鼠在坐骨神经切除后2、4、8和12周，采用自切（自我截肢）评分和神经残端大体和组织学变化评估神经性疼痛。将45只大鼠分为3个实验组，不盖顶（对照组，n = 15）， 3-mm神经导管盖顶（n = 15）， 6-mm神经导管盖顶（n = 15）。所有大鼠在神经切除术后12周采用自切评分和神经残端组织学进行评估。神经导管比大鼠坐骨神经直径1.5 mm大约0.5 mm，以防止神经收缩。结果自体切开术评分随时间延长而逐渐加重。神经切除术后2周，由于随机轴突再生，形成了典型的球根状神经瘤。随后，随着时间的推移，神经瘤周围的粘连扩大了12周，在12周的时间点，无封顶（对照组）组的平均自切评分最高，其次是3和6毫米神经导管组。组织学上，远端轴突纤维变薄并终止于6毫米神经导管内，而它们在3毫米神经导管上延长并突出。在6mm神经导管组，末端轴突纤维周围有少量神经周围瘢痕形成。6 mm神经导管组神经残端抗-平滑肌肌动蛋白和抗-sigma-1受体抗体表达明显降低。结论：在大鼠坐骨神经截肢模型中，生物可吸收神经导管神经盖治疗可缓解神经瘤性神经性疼痛，防止神经残端周围神经瘢痕形成和神经炎症。适当的神经导管长度为原神经直径的4倍以上。
OBJECTIVE Treatment of painful neuroma remains difficult, despite the availability of numerous surgical procedures. Recently, nerve capping treatment for painful neuroma using artificial nerve conduits has been introduced in clinical and basic research. However, the appropriate length of the nerve conduit and the pain relief mechanism have not been determined. In this study the authors aimed to investigate nerve capping treatment with a bioabsorbable nerve conduit using the rat sciatic nerve amputation model. Using histological analysis, the authors focused on the nerve conduit length and pain relief mechanism.METHODS Sixteen Sprague Dawley rats were evaluated for neuropathic pain using an autotomy (self-amputation) score and gross and histological changes of the nerve stump 2, 4, 8, and 12 weeks after sciatic nerve neurectomy without capping. Forty-five rats were divided into 3 experimental groups, no capping (control; n = 15), capping with a 3-mm nerve conduit (n = 15), and capping with a 6-mm nerve conduit (n = 15). All rats were evaluated using an autotomy score and nerve stump histology 12 weeks after neurectomy. The nerve conduit was approximately 0.5 mm larger than the 1.5-mm diameter of the rat sciatic nerves to prevent nerve constriction.RESULTS The autotomy scores gradually exacerbated with time. Without capping, a typical bulbous neuroma was formed due to random axonal regeneration 2 weeks after neurectomy. Subsequently, the adhesion surrounding the neuroma expanded over time for 12 weeks, and at the 12-week time point, the highest average autotomy scores were observed in the no-capping (control) group, followed by the 3- and the 6-mm nerve conduit groups. Histologically, the distal axonal fibers became thinner and terminated within the 6-mm nerve conduit, whereas they were elongated and protruded across the 3-mm nerve conduit. Minimal perineural scar formation was present around the terminated axonal fibers in the 6-mm nerve conduit group. Expressions of anti-alpha smooth muscle actin and anti-sigma-1 receptor antibodies in the nerve stump significantly decreased in the 6-mm nerve conduit group.CONCLUSIONS In the rat sciatic nerve amputation model, nerve capping treatment with a bioabsorbable nerve conduit provided relief from neuroma-induced neuropathic pain and prevented perineural scar formation and neuroinflammation around the nerve stump. The appropriate nerve conduit length was determined to be more than 4 times the diameter of the original nerve.